The effect of repeated intragastric administration of N-nitrosomethylurea on the molar gingival epithelium of the hamster was investigated both histologically and histoautoradiographically. Thickening and downward proliferation of the gingival epithelium were evident from the second month of the treatment, in the attachment epithelium and interdental epithelium. Subsequently, the apical part of the crevicular epithelium, epithelium of the oral aspect of the gingiva, and the marginal crevicular epithelium thickened. About three months after the beginning of the administration, thickening, hyperkeratosis, and downward proliferation of the gingival epithelium were widespread, and proliferated epithelial cell nests were parakeratotic, often assuming a structure of keratotic cyst, which invaded the periodontium, accompanied with compressive resorption of the alveolar bone and involvement of bone marrows. Cellular atypia appeared three months after the fast treatment, occasionally suggesting early malignancy. Epithelial proliferation was generally not accompanied with any distinct inflammatory change. In the autoradiographic analysis, it was clearly noticed that labeled cells had increased in each epithelial zone before the histological changes became evident. The results of the present experiment were discussed in reference to the pathogenesis of gingival carcinoma.
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